N-beta-(3-pyridyl)-ethylmorpholine salt of penicillin



Patented Oct. 6, 1953 UNITED STATES PATENT OFFICE N-fl- (3-PYRIDYL) -ETHYLMORPHOLINE SALT F PEN ICILLIN Harley W. Rhodehamel, Jr., Indianapolis, Ind., assignor to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana No Drawing. Application February 13, 1952, Serial No. 271,431

2 Claims. (Cl. 260-2391) 1 2 This invention relates to a novel pencillin salt ethylmorpholine dihydrochloride in 5 ml. of Waand the preparation thereof. ter. The mixture is cooled and stirred occasion- I have discovered that N-fi-(B-pyridyl) -ethylally whereupon the slightly soluble N-fl-(B- morph-oline or its salts can be combined with pyridyD-ethylmorpholine salt of penicillinGprepenicillin or its salts by neutralization or meta- 5 cipitates. The salt is separated, and dried in thetical reactions to form a sparingly soluble vacuo. penicillin salt, thereby afiording a means of pre- N-fl-(s-pyridyl)-ethylmorpholine can be precipitating penicillin from solution, and of purifypared as follows: 3-pyridylacetothiomorpholide, ing penicillin. Moreover, the novel penicillin salt obtained by the method of Schwenk et 2.1., J. Orcan be utilized therapeutically. A prolonged ganic Chemistry 11,798 (194.6),is desulfurized acpenicillin blood level can b secured upon admincording to the process of Kornfeld, J. Organic istering the salt parenterally by methods known Chemistry 16, 131, (1951), using Raney nickel. to the medical art. The N-[i-(3-pyridyl)-ethylmorpholine which is The following examples illustrate the preparathus obtained forms acid addition salts when tion of th novel salt of this invention: treated by the usual methods.

I claim: Example 1 1. The N- S-(3-pyridyl)-ethylmorpholine salt To 3 g. of a solution of penicillin (e. g. a comof penicillin represented by the following formula mercial mixture of the several penicillins) disin which P represents penicillin: solved in about 50 m1. of amyl acetate are added CH2 OH 3 g. of N,8(3pyridyl) -ethylm0rpholine dissolved 2 in ml. of amyl acetate. The mixture is cooled CECE-1F and stirred occasionally whereupon the N-B-(B- P CH;CH, pyridyD-ethylmorpholine salt of penicillin precipitates. The salt is isolated as by decantation i filtration and dried in vacuo. 25 2. The N-B-(3-pyr1dy1)-ethylmorphol1n salt The salt is represented by the following formula of penicillin in which P represents penicillin: HARLEY RHODEHAMEL,

References Cited in the file of this patent Groom-n 0 UNITED STATES PATENTS P Number Name Date 2,569,666 Granatek Oct. 2, 1951 Example 2 12,578,651 Buckwalter' Dec. 18, 1951 To an aqueous solution of 0.3 g. of the potas- FOREIGN PATENTS slum salt of penicillin G in 1.8 ml. of water is Number Country Date added a solution of 0.3 g. of N-fl-(S-pyridyb- 645,037 Great Britain Oct. 25, 1950 

1. THE N-B-(3-PYRIDYL) -ETHYLMORPHOLINE SALT OF PENICILLIN REPRESENTED BY THE FOLLOWING FORMULA IN WHICH P REPRESENTS PENICILLIN: 